Diabetes, Metabolic Syndrome and Obesity (Sep 2019)
Effect of berberine on the HPA-axis pathway and skeletal muscle GLUT4 in type 2 diabetes mellitus rats
Abstract
Jia Mi,1,* Wenda He,1,* Jiawei Lv,1 Kai Zhuang,1 Heqing Huang,1,2 Shijian Quan1 1School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, People’s Republic of China; 2Laboratory of Pharmacology & Toxicology, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Heqing Huang; Shijian QuanDepartment of School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, No. 232 East Wai Huan Road, Guangzhou 510006, People’s Republic of ChinaTel +86 1 392 211 9719Email [email protected] [email protected]: Activation of the hypothalamus-pituitary-adrenal (HPA) axis pathway is closely related to insulin resistance (IR), glucose, and lipid metabolism disorders in type 2 diabetes mellitus (T2DM). Berberine (BBR) has effect on regulating disorder of glucose and lipid metabolism in T2DM. In fact, activation of the HPA axis pathway is closely related to IR, glucose, and lipid metabolism disorders in T2DM. Here, we investigated whether the therapeutic effect of BBR on T2DM rats is acted through the HPA axis pathway. Methods: In this research, we investigated the effects of BBR on the HPA-axis pathway-related indicators and expression of skeletal muscle glucose transporter 4 (GLUT4) in the high-fat diet and streptozotocin-induced T2DM rats, and identify its possible mechanism of improving IR in T2DM.Results: BBR significantly reduced fasting blood glucose, total cholesterol, and low-density lipoprotein cholesterol in model rats. It also improved the abnormalities of the high-density lipoprotein cholesterol, the insulin resistance index, the insulin sensitivity index, glucagon, and insulin levels. BBR decreased levels of hypothalamic Orexin-A, the OX2R receptor, the corticotropin-releasing hormone, the pituitary and the plasma adrenocorticotropic hormone, as well as serum and urine corticosterone. At the same time, BBR increased mRNA and protein expressions of GLUT4 in skeletal muscles of model rats as well.Conclusion: Those results suggested that BBR can exert inhibition on the HPA-axis and increased skeletal muscle expression of GLUT4 proteins, which may be one of the important mechanisms in BBR to improve IR and regulating glucose and lipid metabolism in T2DM rats.Keywords: berberine, type 2 diabetes mellitus, insulin resistance, the HPA-axis, GLUT4
